Protein-Templated Dynamic Combinatorial Chemistry: Brief Overview and Experimental Protocol

Alwin M Hartman; Robin M Gierse; Anna K H Hirsch

doi:10.1002/ejoc.201900327

Protein-Templated Dynamic Combinatorial Chemistry: Brief Overview and Experimental Protocol

European J Org Chem. 2019 Jun 16;2019(22):3581-3590. doi: 10.1002/ejoc.201900327. Epub 2019 May 29.

Authors

Alwin M Hartman^{1

2

3}, Robin M Gierse^{1

2

3}, Anna K H Hirsch^{1

2

3}

Affiliations

¹ Department of Drug Design and Optimization Helmholtz Institute for Pharmaceutical Research Saarland (HIPS) Helmholtz Centre for Infection Research (HZI) Campus Building E8.1 66123 Saarbrücken Germany.
² Stratingh Institute for Chemistry Helmholtz Centre for Infection Research (HZI) University of Groningen Nijenborgh 7 9747 AG Groningen The Netherlands.
³ Department of Pharmacy Medicinal Chemistry Saarland University Campus Building E8.1 66123 Saarbrücken Germany.

Abstract

Dynamic combinatorial chemistry (DCC) is a powerful tool to identify bioactive compounds. This efficient technique allows the target to select its own binders and circumvents the need for synthesis and biochemical evaluation of all individual derivatives. An ever-increasing number of publications report the use of DCC on biologically relevant target proteins. This minireview complements previous reviews by focusing on the experimental protocol and giving detailed examples of essential steps and factors that need to be considered, such as protein stability, buffer composition and cosolvents.

Keywords: Biochemical activity; Hit identification; Medicinal chemistry; Protein stability; Target‐directed dynamic combinatorial chemistry.

Publication types

Review